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Hemophilia is caused by a lack of antihemophilic factor(s), for example, factor VIII (FVIII; hemophilia A) and factor IX (FIX; hemophilia B). Low bone mass is widely reported in epidemiological studies of hemophilia, and patients with hemophilia are at an increased risk of fracture. The detailed etiology of bone homeostasis imbalance in hemophilia is unclear. Clinical and experimental studies show that FVIII and FIX are involved in bone remodeling. However, it is likely that antihemophilic factors affect bone biology through thrombin pathways rather than via their own intrinsic properties. In addition, among patients with hemophilia, there are pathophysiological processes in several systems that might contribute to bone loss. This review summarizes studies on the association between hemophilia and bone remodeling, and might shed light on the challenges facing the care and prevention of osteoporosis and fracture in patients with hemophilia.Epigenetics, a term conventionally used to explain the intricate interplay between genes and the environment, is now regarded as the fundament of developmental biology. Several lines of evidence garnered over the past decades suggest that epigenetic alterations, mostly encompassing DNA methylation, histone tail modifications, and generation of microRNAs, play an important, though still incompletely explored, role in both primary and secondary hemostasis. Epigenetic variations may interplay with platelet functions and their responsiveness to antiplatelet drugs, and they may also exert a substantial contribution in modulating the production and release into the bloodstream of proteins involved in blood coagulation and fibrinolysis. This emerging evidence may have substantial biological and clinical implications. An enhanced understanding of posttranscriptional mechanisms would help to clarify some remaining enigmatic issues in primary and secondary hemostasis, which cannot be thoughtfully explained by genetics or biochemistry alone. Increased understanding would also pave the way to developing innovative tests for better assessment of individual risk of bleeding or thrombosis. The accurate recognition of key epigenetic mechanisms in hemostasis would then contribute to identify new putative therapeutic targets, and develop innovative agents that could be helpful for preventing or managing a vast array of hemostasis disturbances.New emerging evidence is now prompting researchers to devote greater focus on the roles played by red blood cells (RBCs) in hemostasis. This short narrative review aims to outline the available research, past and current, that has revealed the role of RBCs in hemostasis, particularly blood clotting. Although early researchers suggested that RBCs were involved in blood clotting, they had insufficient evidence to support such claims. As a result, this area of research received little attention from other scientists. Early researchers primarily used quantitative measures of RBCs, namely hematocrit or RBC count, as higher numbers of RBCs modulate blood rheology by increasing viscosity. Recent research has instead shed light on the different measures of RBC function, such as expression of phosphatidylserine and adhesive proteins, aggregation, hemolysis, release of extracellular microvesicles, and erythrocyte volume. RBCs play a role in the contraction of clots by platelets, and the resulting densely packed array of polyhedral erythrocytes forms an almost impermeable barrier that is essential for hemostasis and wound healing. Renewed interest in RBCs is primarily due to the clinically and experimentally established relationships between erythrocytes and hemostasis, which have suggested that erythrocytes are potential targets for the treatment of hemostatic disturbances.The role of rivaroxaban in the treatment of leg superficial venous thrombosis (SVT) is uncertain. This article aims to determine if rivaroxaban is an effective and safe treatment for leg SVT. Patients with symptomatic leg SVT of at least 5 cm length were randomized to 45 days of rivaroxaban 10 mg daily or to placebo, and followed for a total of 90 days. Treatment failure (required a nonstudy anticoagulant; had proximal deep vein thrombosis or pulmonary embolism; or had surgery for SVT) at 90 days was the primary efficacy outcome. Secondary efficacy outcomes included leg pain severity, and venous disease-specific and general health-related quality of life over 90 days. Major bleeding at 90 days was the primary safety outcome. Poor enrollment led to the trial being stopped after 85 of the planned 600 patients were randomized to rivaroxaban (n = 43) or placebo (n = 42). One rivaroxaban and five placebo patients had a treatment failure by 90 days (absolute risk reduction = 9.0%, 95% confidence interval -22 to 5.9%). Leg pain improvement did not differ at 7 (p = 0.16) or 45 days (p = 0.89), but was greater with rivaroxaban at 90 days (p = 0.011). There was no difference in venous disease-specific (p = 0.99) or general health-related (p = 0.37) quality of life over 45 days. There were no major bleeds or deaths in either group. There were no identifiable differences in efficacy or safety between rivaroxaban and placebo in patients with symptomatic SVT but comparisons were undermined by a much smaller than planned sample size (NCT1499953).Anticoagulants are frequently used as thromboprophylaxis and in patients with atrial fibrillation (AF) or venous thromboembolism (VTE). While obesity rates are reaching epidemic proportions worldwide, the optimal dosage for obese patients has not been established for most anticoagulants, including low-molecular-weight heparin (LMWH), non-vitamin K antagonist oral anticoagulants (NOAC), and pentasaccharides (fondaparinux). The aim of the present systematic review was to summarize the current knowledge and provide recommendations on dosage of LMWH, NOAC, and fondaparinux in obese patients (body mass index [BMI] ≥ 30 kg/m2 or body weight ≥ 100 kg). Based on a systematic search in PubMed and Embase, a total of 72 studies were identified. For thromboprophylaxis with LMWH in bariatric surgery (n = 20 studies), enoxaparin 40 mg twice daily, dalteparin 5,000 IE twice daily, or tinzaparin 75 IU/kg once daily should be considered for patients with BMI ≥ 40 kg/m2. For thromboprophylaxis with LMWH in nonbariatric surgery and in medical inpatients (n = 8 studies), enoxaparin 0.5 mg/kg once or twice daily or tinzaparin 75 IU/kg once daily may be considered in obese patients. For treatment with LMWH (n = 18 studies), a reduced weight-based dose of enoxaparin 0.8 mg/kg twice daily should be considered in patients with BMI ≥ 40 kg/m2, and no dose capping of dalteparin and tinzaparin should be applied for body weight  100 kg.A large volume of literature has become available to practitioners prescribing anticoagulants. The aim of this study was to analyze the bibliometric characteristics of the top 100 most cited articles related to anticoagulation over the past 25 years, with special consideration to impact of direct or "nonvitamin K antagonist" oral anticoagulants (NOACs) compared with vitamin K antagonists. A bibliometric analysis of the 100 most cited journal articles related to anticoagulants published between 1994 and 2019 was performed in April 2019. The top 100 articles by citation count were analyzed to extract bibliometric data related to journal title, impact factor, year of publication, place of publication, anticoagulant studied, indication for anticoagulation, study design, and conflicts of interest. The median (interquartile range) number of citations per article was 806 (621-1,085). The anticoagulant most frequently researched was warfarin (37%). NOAC publications (21%) grew at a relative rate of 3.4 times faster compared with all publications. The indication most commonly researched was venous thromboembolism (26%). Eighty articles constituted level I or II evidence, with randomized controlled trials the most common type of study (74). A financial conflict of interest was declared in 87% of articles with private, for-profit organizations the most common source of funding (26%). In summary, top research related to anticoagulation is highly impactful but may be at risk of sponsorship bias. High-level evidence for NOACs continues to expand across a range of indications with citation metrics likely to soon approach or surpass that of older drugs.Prompt diagnosis of pulmonary embolism (PE) remains challenging, which often results in a delayed or inappropriate treatment of this life-threatening condition. Mobile thrombus in the right cardiac chambers is a neglected cause of PE. It poses an immediate risk to life and is associated with an unfavorable outcome and high mortality. Thrombus residing in the right atrial appendage (RAA) is an underestimated cause of PE, especially in patients with atrial fibrillation. This article reviews achievements and challenges of detection and management of the right atrial thrombus with emphasis on RAA thrombus. The capabilities of transthoracic and transesophageal echocardiography and advantages of three-dimensional and two-dimensional echocardiography are reviewed. Strengths of cardiac magnetic resonance imaging (CMR), computed tomography, and cardiac ventriculography are summarized. We suggest that a targeted search for RAA thrombus is necessary in high-risk patients with PE and atrial fibrillation using transesophageal echocardiography and/or CMR when available independently on the duration of the disease. High-risk patients may also benefit from transthoracic echocardiography with right parasternal approach. The examination of high-risk patients should involve compression ultrasonography of lower extremity veins along with the above-mentioned technologies. Algorithms for RAA thrombus risk assessment and protocols aimed at identification of patients with RAA thrombosis, who will potentially benefit from treatment, are warranted. The development of treatment protocols specific for the diverse populations of patients with right cardiac thrombosis is important.Atrial fibrillation (AF) can be secondary to acute pulmonary embolism (PE). This study aimed to investigate the prognostic impact of new-onset AF on patients with acute PE. In this study, 4,288 consecutive patients who were diagnosed with acute PE were retrospectively screened. In total, 77 patients with acute PE and new-onset AF were analyzed. Another 154 acute PE patients without AF were selected as the age- and sex-matched control group. Adverse in-hospital outcome comprised one of the following conditions all-cause death, endotracheal intubation, cardiopulmonary resuscitation, and intravenous catecholamine therapy. The patients with new-onset AF had higher prevalence of congestive heart failure, higher simplified PE severity index (sPESI), higher creatinine, and larger left atrium diameter. this website The incidences of adverse in-hospital outcomes were 10.4 and 2.6% in patients with new-onset AF and no AF, respectively (p = 0.02). Patients with sPESI ≥ 1 had higher incidence of adverse in-hospital outcomes than those with sPESI = 0 (9.4 vs. 0.9%, p  less then  0.01). The area under the receiver operating characteristic curve of sPESI and sPESI + AF (adding 1 point for new-onset AF) scores in assessing the adverse in-hospital outcome were 0.80 (95% confidence interval [CI] 0.68-0.93) and 0.84 (95% CI 0.72-0.96), respectively. In multivariable analysis, sPESI ≥ 1 (odds ratio, 8.88; 95% CI 1.10-72.07; p = 0.04) was an independent predictor of adverse in-hospital outcome. However, new-onset AF was not an independent predictor. In the population studied, sPESI is an independent predictor of adverse in-hospital outcomes, whereas new-onset AF following acute PE is not, but it may add predictive value to sPESI.
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